Role of chemokines in promoting instability of coronary atherosclerotic plaques and the underlying molecular mechanism

Abstract

Our aim was to investigate the role of chemokines in promoting instability of coronary atherosclerotic plaques and the underlying molecular mechanism. Coronary angiography and intravascular ultrasound (IVUS) were performed in 60 stable angina pectoris (SAP) patients and 60 unstable angina pectoris (UAP) patients. The chemotactic activity of monocytes in the 2 groups of patients was examined in Transwell chambers. High-sensitivity C-reactive protein (hs-CRP), monocyte chemoattractant protein-1 (MCP-1), regulated on activation in normal T-cell expressed and secreted (RANTES), and fractalkine in serum were examined with ELISA kits, and expression of MCP-1, RANTES, and fractalkine mRNA was examined with real-time PCR. In the SAP group, 92 plaques were detected with IVUS. In the UAP group, 96 plaques were detected with IVUS. The plaques in the UAP group were mainly lipid 51.04% (49/96) and the plaques in the SAP group were mainly fibrous 52.17% (48/92). Compared with the SAP group, the plaque burden and vascular remodeling index in the UAP group were significantly greater than in the SAP group (P<0.01). Chemotactic activity and the number of mobile monocytes in the UAP group were significantly greater than in the SAP group (P<0.01). Concentrations of hs-CRP, MCP-1, RANTES, and fractalkine in the serum of the UAP group were significantly higher than in the serum of the SAP group (P<0.05 or P<0.01), and expression of MCP-1, RANTES, and fractalkine mRNA was significantly higher than in the SAP group (P<0.05). MCP-1, RANTES, and fractalkine probably promote instability of coronary atherosclerotic plaque.

Serum C‐reactive protein in the prediction of cardiovascular diseases: Overview of the latest clinical studies and public health practice

“…-Current knowledge suggests that serum hs-CRP could be useful to estimate the risk of plaque rupture (De Rosa et al, 2017;Hong et al, 2011) and the vulnerability of the atheromatous lesion (Libby, 2006;Zhong et al, 2015). In contrast, none of the other systemic markers of inflammation, such as upstream cytokine mediators, sensitive acute-phase proteins, negative acute-phase proteins, or cruder multifactorial measures, have such robust and desirable characteristics (Marks & Neill, 2007;Shrivastava et al, 2015).…”

“…In addition, clinical trials and epidemiological studies have found that there is no significant difference and diurnal variation in the distribution curve between women and men, and its serum concentrations are independent of ethnicity and age (Shrivastava et al, ; Xu et al, ). A large number of in vivo and vitro studies have found that serum CRP is a strong independent predictor of future CVD risk and events (Alzalzalah, ; Gupta, Gupta, Gupta, Arora, & Gupta, ). The attention focused on CRP reflects a strong correlation between elevated plasma levels of CRP and the risk of future atherothrombotic events (Chandrashekara, ; Wilson et al, ), including stroke (Elkind et al, ; Idicula et al, ), coronary events (Christiansen, ; Shah et al, ; Shrivastava et al, ), and peripheral arterial disease (Gupta et al, ; Inoue et al, ). Current knowledge suggests that serum hs‐CRP could be useful to estimate the risk of plaque rupture (De Rosa et al, ; Hong et al, ) and the vulnerability of the atheromatous lesion (Libby, ; Zhong et al, ). In contrast, none of the other systemic markers of inflammation, such as upstream cytokine mediators, sensitive acute‐phase proteins, negative acute‐phase proteins, or cruder multifactorial measures, have such robust and desirable characteristics (Marks & Neill, ; Shrivastava et al, ). Recent studies have shown that plasma CRP concentrations predict the risk of the metabolic syndrome because components of the metabolic syndrome (i.e., central obesity, hypertension, low plasma concentrations of high‐density lipoprotein (HDL), increased plasma triglyceride concentrations, and increased concentrations of blood glucose) correlate with increased plasma CRP concentrations (Hoogeveen et al, ; Shrivastava et al, ; Tully et al, ). Current studies suggested that exercise, weight loss, smoking cessation, diet, and diabetes control also reduce serum CRP levels (Church et al, ).…”

Large Extracellular Vesicle-Associated Rap1 Accumulates in Atherosclerotic Plaques, Correlates With Vascular Risks and Is Involved in Atherosclerosis

“…20 Levels of lEVs carrying Rap1 also correlated with levels of hs-CRP which is a described marker to estimate the risk of plaque instability 21 and vulnerability of atheromatous lesion. 22 To corroborate this, lEVs carrying Rap1 were also correlated with right common carotid EDV, which is associated with a high probability to develop stenosis. 23 All these clinical data strongly support that circulating levels of lEVs harboring Rap1 could be useful to evaluate the risks of developing cardiovascular events in MetS patients.…”

Fractalkine Signalling (CX3CL1/CX3CR1 Axis) as an Emerging Target in Coronary Artery Disease

“…Several studies have looked at the relevance of sFKN as well as CX 3 CR1-expressing cells in the context of plaque rupture. Using intracoronary imaging methodology of either intravascular ultrasound (IVUS) or optical coherence tomography (OCT) to understand plaque morphology, studies have compared the levels of FKN and their corresponding receptors to the instability of plaque disease [48][49][50]. Patients with unstable angina and proven unstable plaque disease were found to have significantly higher levels of FKN and mononuclear cells expressing CX 3 CR1, as compared to stable angina patients or healthy controls.…”